Neurofibromatosis 1 (NF-1) is an autosomal dominant genodermatosis with an increased risk of developing mesenchymal malignancies. A 28-year-old woman with NF-1 was admitted to our Department for deep ulcers on the right thigh. The ulcerations had appeared about two years earlier, and were initially diagnosed as pyoderma gangrenosum. The patient received immunosuppressive therapy but only marginal improvement was observed. Several months later, the disease progressed, so a skin biopsy was taken, establishing cytophagic histiocytic panniculitis. The patient was admitted to our Department for further therapy. After re-evaluation of histological slides, while taking into account the clinical presentation and previously established histological diagnosis, subcutaneous panniculitis-like T cell lymphoma (SPTL) was diagnosed. Chemotherapy (combination of fludarabine and cyclophosphamide) was started, resulting in almost complete remission of malignant lesions. To the best of our knowledge, this is the first report of the development of SPTL in NF-1.